title: Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties.
abstract: BACKGROUND
  There is increasing interest in antipsychotics intended to manage positive symptoms via D(2) receptor blockade and improve negative symptoms and cognitive deficits via 5-HT(1A) activation. Such a strategy reduces side-effects such as the extrapyramidal syndrome (EPS), weight gain, and autonomic disturbance liability.
  
  
  OBJECTIVE
  This study aims to review pharmacological literature on compounds interacting at both 5-HT(1A) and D(2) receptors (as well as at other receptors), including aripiprazole, perospirone, ziprasidone, bifeprunox, lurasidone and cariprazine, PF-217830, adoprazine, SSR181507, and F15063.
  
  
  METHODS
  We examine data on in vitro binding and agonism and in vivo tests related to (1) positive symptoms (e.g., psychostimulant-induced hyperactivity or prepulse inhibition deficit), (2) negative symptoms (e.g., phencyclidine-induced social interaction deficits and cortical dopamine release), and (3) cognitive deficits (e.g., phencyclidine or scopolamine-induced memory deficits). EPS liability is assessed by measuring catalepsy and neuroendocrine impact by determining plasma prolactin, glucose, and corticosterone levels.
  
  
  RESULTS
  Compounds possessing "balanced" 5-HT(1A) receptor agonism and D(2) antagonism (or weak partial agonism) and, in some cases, combined with other beneficial properties, such as 5-HT(2A) receptor antagonism, are efficacious in a broad range of rodent pharmacological models yet have a lower propensity to elicit EPS or metabolic dysfunction.
  
  
  CONCLUSIONS
  Recent compounds exhibiting combined 5-HT(1A)/D(2) properties may be effective in treating a broader range of symptoms of schizophrenia and be better tolerated than existing antipsychotics. Nevertheless, further investigations are necessary to evaluate recent compounds, notably in view of their differing levels of 5-HT(1A) affinity and efficacy, which can markedly influence activity and side-effect profiles.
authors.affiliation: NeuroAct Communication, Castres, France. adrian.newman.tancredi@neuroact.com
authors.forename: Adrian
authors.initials: A
authors.lastname: Newman-Tancredi
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kleven
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D058825:Serotonin 5-HT1 Receptor Agonists